Plants that changed the world: cinchona

Tom Freeman looks at the Peruvian tree that gave us the first effective treatment for malaria – as well as a refreshing drink

In the early 1600s, Spanish colonists in Peru had perhaps the biggest stroke of luck in the history of medicine. They noticed that the indigenous Quechua people used the bark of the local cinchona tree, ground up and added to water, to relieve shivering.

Shivering is a major sign of the deadly recurring fever – then called ague and now known as malaria – that European doctors had long struggled to fight, so the Spaniards decided to try cinchona.

The Quechua’s shivers were nothing to do with malaria, which wasn’t native to the Americas. Knowing this, there would have been no reason to expect the bark to work against an unrelated infection. But it did. It could both cure and prevent malaria.

Saving lives is big business

Cinchona trees (there are at least 23 species in the Cinchona genus) are native to the slopes of the Andes. They’re evergreen, have a red-pink blossom and can grow up to 30 metres tall. And they made a fortune for the Spanish Empire.

Once the Spaniards realised the bark’s power, they built an industry around it. Massive logging of cinchona trees got underway, and fleets of ships carried the bark to Europe for sale. Doctors were sceptical at first, but ultimately they couldn’t argue with the results: among the huge numbers of people saved from malaria were King Charles II of England and Louis XIV of France.

Cinchona bark didn’t just defeat malaria in Europe. It also meant Europeans could survive in parts of Africa and Asia where malaria was rampant. The fruits of one empire enabled the spread of others.

The Spanish went to great lengths to keep their monopoly, but eventually, Dutch and British explorers managed to smuggle cinchona out of South America and started their own plantations.

Quinine: the drug inside the bark

What’s in cinchona that makes it so effective? The answer came from two French chemists, Pierre Pelletier and Joseph Caventou, in 1820. They isolated several alkaloids (nitrogen-containing bases) from the bark, most notably quinine. This was the crucial antimalarial agent, and its discovery allowed treatment to become more efficient: irrelevant ingredients could be removed and doses could be standardised.

How, then, does quinine work against the Plasmodiumparasites that cause malaria? We still don’t quite know, although we do know what stage of the infection it disrupts.

When Plasmodium gets into human blood, it devours the protein haemoglobin, creating the iron-containing compound haeme as a by-product. Haeme, though, is toxic to Plasmodium, so the parasite converts it into an unreactive crystal form that doesn’t pose any harm. What quinine seems to do – somehow – is prevent this crystallisation, so the Plasmodium parasites poison themselves as they eat and die before they can do serious harm.

There were other useful alkaloids in the bark too: quinidine, for instance, can treat heart irregularities (arrhythmia). Others have found uses in chemistry as catalysts.

Helping the medicine go down

Quinine tastes bitter. So, to make their doses more appealing, British colonials in India hit upon the idea of mixing their quinine water with gin and lemon. This healthy, restorative drink became known as the gin and tonic, and to this day tonic water is made with quinine. This is why on many of the ‘soda guns’ that bartenders use, the tonic button is marked with a Q.

You can’t treat malaria with tonic water, though: it contains very little quinine. To get a single day’s dose, you would need to drink 30 litres of Schweppes Indian Tonic Water – after which malaria would be the least of your problems.

Quinine in the 21st century

After 300 years as the world’s leading malaria treatment, quinine has fallen from favour. During the 20th century, strains of Plasmodium evolved that could resist its effects. Luckily, in the 1970s, scientists in China isolated the drug artemisinin from the sweet wormwood plant – also long used in traditional medicine, and very effective against malaria.

Today, artemisinin is the World Health Organization’s main recommended antimalarial drug. But for women in early pregnancy, its possible side-effects mean that quinine may still be preferred. It can also be used if artemisinin is unavailable.

Quinine isn’t just an antimalarial, though. It’s also a muscle relaxant (which may explain its value to the Quechua), and the NHS and other health systems still use it to treat cramps.

Figures on quinine production vary, but one 2009 estimate is that 700 tonnes of alkaloids are extracted from cinchona bark every year. Roughly half of this is used medically and the other half by the food and drink industry.

Questions for discussion

What ethical issues are raised by the mass commercial use of traditional community medicines?

Why might European doctors have been reluctant at first to accept this impressive new treatment?

Read the interview with the CEO of a major quinine producer (part 2 of ‘From pharmacy to the pub’ in the references above). What are some of the practical problems in getting a drug from cinchona trees?

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Watch or download our animation exploring the action of indole-3-acetic acid (IAA), the most common form of auxin, and which looks at how scientists used experimental evidence to explain the role of auxins in a phototrophic response

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